Tag Archives: osteonecrosis

This column last considered bisphosphonates BPN in February. This reviews some new papers published since.

ADVANCED CANCER with bone spread: Recent major (Cochrane) reviews confirm that BPNs may be valuable in advanced prostate and breast cancer , for reducing skeletal events and maybe pain, although they do not clearly influence disease progression or patient survival.

OSTEOPOROSIS: It is now almost 5 years since the balloon went up on the unnecessary major risks of BPN for osteoporosis. So anyone who was prescribed these dangerous drugs since then for osteoporosis, without the rare special indications, and who develops BNP-related complications (or osteoporosis-related fractures) has a strong case for heavy damages against the prescriber, the dispensing pharmacy and regulator eg the State clinic or medical plan who/which advised/ allowed use of the drug for that condition. .

Bisphosphonates were invented over a century ago but developed over the last 40years for clinical treatment of metabolic bone diseases, with the first human trials reported about 35 years ago (Heaney 1976). Why have they been exhaustively tested and now routinely used for prevention and treatment of aging osteoporosis, despite their considerable cost especially risks, and lack of global benefit?

Obviously because as patented designer drugs they are profitable to the Disease Industry – despite the fact that their biggest section on Wiki is about their rare but major adverse effects- to quote Wiki :

Intravenous BPN can give fever and flu-like symptoms after the first infusion. The slightly increased risk for electrolyte disturbances is not enough to warrant regular monitoring.

BPN have been associated with osteonecrosis of the jaw – the mandible twice as frequently affected as the maxilla- and most cases occurring following high-dose intravenous administration for cancer patients. Some 60% of cases are preceded by a dental surgical procedure (that involve the bone).

Matrix metalloproteinase 2 may be a candidate gene for BPN-associated ONJ since it is the only gene known to be associated with bone abnormalities and atrial fibrillation, both of which are side effects of BPN.

Long-term BPN use resulting in severe or over suppression of bone turnover especially at the femur sub-trochanteric region. Micro-cracks in the bone maybe unable to heal and eventually unite and propagate, resulting in atypical fractures, which tend to heal poorly and often require some form of bone stimulation eg bone grafting.

NO COMPELLING INDICATIONS FOR BPN IN OSTEOPOROSIS: the Wiki entries for BPN and osteoporosis are cleverly written by BPN promoters / marketeers – they fails to justify why BPNs are “the most popular first-line drug”… and the overwhelming evidence that favours combined natural supplements: eg that in the Womens Health Initiative, appropriate hormone replacement HRT ie started soon after menopause is safe up to 10 years of use, halved fracture rate and colon cancer, and lowered all other chronic major degenerative diseases AND breast cancer AND premature deaths by a third. BPNs have risks but no benefits other than fracture reduction- ie for osteoporosis, no compelling indications and the legal eagles are hungry.. .

Italy now reports increase in hypocalcemia and raised serum creatinine ie kidney impairment after BPN for cancer . . Sweden reports no benefit of 2 years’ BPN on knee prosthesis migration. The incidence of metabolic bone disease and all other system complications in intensive care is notorious – and a Princeton report gives no justification for BPN use in ICU when all the safe natural supplements are essential and ensure better protection globally..

A Canadian study shows that ” managed intervention” after osteoporotic hip fracture prevented 4 new hip fractures and gained 4 quality life-years – but the available abstract omits what the interventions were, and whether survival was increased.

And while all rational evidence-based appropriate prevention and treatment of osteoporosis – the permanent baker’s dozen of safe natural supplements- reduce all-cause chronic degenerative disease and mortality by at least a third, without any risks, – BPNs have increasingly recorded risks both short term and long term, with no extraskeletal benefits, despite reducing the fracture risk (spine -Cummings 2002; hip Nguyen 2006) by up to a half.

OSTEONECROSIS OF THE JAW ONJ: first reported in 2003, only 26 cases of ONJ on oral BPN could be found reported worldwide up to Sept 2006 in a 2007 University Pennsylvania study . Only 15 % were men, and the majority involved the mandible. Now Israel alone reports another 100 cases of BNP- related jaw osteonecrosis – fossy jaw – and 16% were on oral BPN. The incidence of OJN is speculated to be between 5% and 11% in cancer patients treated with BPN.

A world-wide panel produced the 2008 Canadian Consensus Practice Guidelines for BNP Associated Osteonecrosis of the Jaw, but did not estimate the incidence of ONJ. It concludes that “High-dose intravenous BNP have been identified as a risk factor for ONJ in the oncology patient population. Low-dose BNP use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ” “BPNs have become a cornerstone in the management of skeletal complications of malignancy as well as osteoporosis and metabolic bone disease, as these agents offer tremendous benefit to those with malignancy or metabolic bone disease” Due to limited and misleading public information regarding ONJ, many patients have discontinued BPN treatment, resulting in inadequate care of the underlying skeletal condition.”

But the Canadian Consensus paper fails to clarify in what way BPN offers “tremendous benefit” to those with osteoporosis? The consensus of the majority of practitioners who do not recommend BPN for osteoporosis is that evidence still shows that appropriate HRT with other standard supplements is the best prevention and treatment not just of osteoporosis but of all the common major degenerative diseases of aging. (The International Menopause Society). This eternal truth and aim- the wellbeing of seniors- is the imperative, not the wishful thinking of Big Pharma to replace natural supplements with designer magic bullets for each disease.

Intravenous (IV) BPN are primarily used and effective in treatment and management of cancer-related conditions including hypercalcemia of malignancy, bone metastases such as breast, prostate and lung cancer, and multiple myeloma- for which the clinical efficacy of IV BPN is well established.

BPN have not been shown to improve cancer-specific survival, but they have had a significant positive effect on the quality of life for patients with advanced cancer involving the skeleton.

Oral BPN: By far the most prevalent and common indication is osteoporosis and osteopenia. They are also used for a variety of less common conditions such as Paget’s disease of bone, and osteogenesis imperfecta of childhood.

INCIDENCE OF BRONJ: Based on case series, case-controlled and cohort studies, estimates of the cumulative incidence of BRONJ range from 0.8%-12%.

ORAL BPN BRONJ: Surveillance data from Australia estimated the incidence of BRONJ for patients treated weekly with alendronate as 0.01-0.04%. In a survey study of over 13, 000 Kaiser-Permanente members, the prevalence of BRONJ in patients receiving long-term oral BPN therapy was reported at 0.06% (1:1,700).

Demographic and systemic factors: In the original Position Paper, age, race, and cancer diagnosis with or without osteoporosis were reported as risk factors for BRONJ. Seven studies report increasing age as consistently associated with BRONJ. Sex was not statistically associated with BRONJ. Other systemic factors or conditions, i.e., renal dialysis, low hemoglobin, obesity, and diabetes, were variably reported to increase the risk for BRONJ. Malignancy type was not statistically associated with an increased risk for BRONJ.

Preventative factors The AAOMS Taskforce on BRONJ recommended that patients undergo dental evaluations and receive necessary treatment prior to initiating IV BPN therapy. In addition, given the long-term biologic activity of IV BPN one may hypothesize that different dosing regimens may be equally effective and decrease the risk for BRONJ.

Using a retrospective cohort study design, Coso et al, evaluated the BRONJ and skeletal-related events e.g. pathologic fracture in multiple myeloma patients using different dosing schedules for zoledronate. These findings suggest that alternative dosing schedules that reduce IV BPN exposure have comparable outcomes in terms of preventing SREs and a decreased risk of BRONJ.

The effectiveness of hyperbaric oxygen therapy as an adjunct to non-surgical and surgical treatment is under investigation at two institutions where a randomized controlled trial is underway. Preliminary results have shown some improvement in wound healing and long-term pain scores, but its use as the sole treatment modality for BRONJ cannot be supported at this time.

Yet despite the fact that osteoporosis and fractures are closely related to and occur along with the major causes of aging disability and premature death – 20% of osteoporotic hip fracture victims die within a year- BPNs have not been shown to reduce any let alone all the other aging diseases let alone premature deaths. The closest a study came to assess the issue was a Singapore analysis of the 30year old clodronate used for up to 2-3 years after breast cancer – which drug showed no influence on overall survival.

This failure of global benefit of BPNs – which are in fact never indicated except rarely eg as palliation in preterminal cancer bone lesions – raises the question of criminal negligence when doctors prescribe and medical schemes and Regulators allow BPN use for osteoporosis. Why are BPNs allowed and prescribed when they have no global benefit but numerous serious risks; and when conventional lowcost natural supplements combined do nothing but global good. eg essential fish oil, essential vigorous-dose blend of vitamins-minerals-biologicals-herbs, essential appropriate HRT , and essential galega-metformin in the overweight let alone obese each lower all-cause chronic morbidity and death by a third to a half.

It is no defence that adverse effects are rare when they are sometimes deadly, and never worth the risk of these drugs since there is rarely overwhelming need to prescribe such drugs- for which there are safe natural and far more effective alternatives.

CASE REPORTS: In 2007 we saw a well-built physically active woman of 61years, whose bone density had fallen some 9% on regular DEXA screening since menopause despite the usual calcium-vitamin D supplement. In 2008 she decided to delay HRT because of strong family history of breast cancer. A year later at followup DEXA on just fish oil plus a modest dose of the standard HealthSpan For-Bone supplement blend (calmag zinc boron manganese; proline; and vits B6-9-12 – C- D3 & K2), her DXA BMD has risen 2% (2.5% at the spine, 1.5% at the hip).

A small slim 61year old bookkeeper presented a year ago on just calcium & vitamin D, her 2007 DEXA spinal density 0.99 having fallen 1% from 2005 ie T -1.6 but her hip down 6.3% from 0.792 to 0.764 ie T-2. Since then, on the Bone Blend and a little estrogen-progesterone-testosterone cream daily, her spine has stayed constant but her hip BMD has risen 2.4% to 0.783.

A new review from Toulouse France has the last word: “Postmenopausal osteoporosis is a chronic disease which justifies long-term treatment. Efficacious available modern fracture-reducing drugs raise the question of the best treatment strategy in postmenopausal women . In this regard, HRT, which allows a more global approach to the menopause-induced consequences of hormone deficiency than the sole prevention of osteoporosis, should be privileged… Use of BPN or strontium ranelate should be thus (at best) be reserved for a more advanced age, when the prevention of hip fracture becomes mandatory“. .

Yet, because it is profitable, the fashion grows to treat the elderly with grossly expensive designer oral strontium, or designer injections of BNP or hormone analogues (of calcitonin or parathormone) – despite the fact that these experimental agents have no extra-skeletal benefits (ie improving cardiovascular, muscle, immune, brain function), have never been tested in longterm studies for at least 6-10 years to test their safety as has eg HRT in the Nurses’ and WHI studies.

But millions of years of bipedal evolution, and numerous studies over the past century, show that all that is required to maintain maximum mobility, mind and mood to enjoy life is lifelong supplements as listed above, appropriate to youth, parents, the middle-aged and seniors.. including healthy seniors’ sexuality. It is too late postponing prevention till wished-for healthy advanced age- which most do not reach due to early demise, or irreversible crippledom from largely avoidable fractures, strokes, heart failure, arthritis, or dementia.

The Israelis’ maxillofacial team lament that “Solutions for decreasing morbidity and poor outcome of ONJ remain elusive.” The answer is painfully obvious: avoid iatrogenic ONJ by avoiding BPN -even orally- except for advanced cancer with bone metastases, but back up lower dose BPN with all the anabolic supplements.

A risk of “only” 7 in 10 000 may reassure a patient being offered BPN for osteoporosis- but if she decides to sue for damages for prescription of totally unnecessary hazardous therapy, the prescriber doesnt have a leg to stand on when the gold standard is appropriate titrated supplements (including HRT) without risks since they reduce all risk by at least one-third.

As wise Chinese taught 2600 years ago, Society, Authorities, Regulators, health professionals have a sacred obligation to above all else prevent avoidable premature death and crippledom with the freely available and low-cost well-proven natural supplements. These must prevail despite the best efforts of Big Business, Big Pharma and their academic and political lobbyists (Governments, Regulators) worldwide to ignore if not outright suppress safe effective old natural supplements (as the FDA and EU are doing) in favour of Diseases and Modern Drugs that Pay – but do not reduce all-cause disease and mortality .

Again we must ask: why are patients with cancer, let alone those with “simply” osteoporosis, given bisphosphonates?

Body’s review from Belgium in 2006 sums up the belief system created by the Disease industry: – cancer patients are given it for osteoporosis, or for metastatic bone disease with high blood calcium.

Yet a new paper from Gutenberg University Germany (Al-Nawas ea) shows that 1 in 20 ie 5% of 75 women with breast cancer given bisphosphonate between 2000 and 2006 developed osteonecrosis of the jaw. That’s just the severe cases identified.

The far bigger study from St Louis & Arkansas Universities last year (Wang-Gillam ea) surely gives the answer for most cases: why give toxic bisphosphonates which do not address the underlying pathogenesis- when this is always multifactorial. They showed that, as in osteoporosis without cancer, most such patients have simple easily correctable deficiency of vitamin D let alone many other universally deficient supplements. They found that “of 321 women with breast cancer given bisphosphonate, 267 were taking the drug for osteoporosisand 54 were taking the drug for metastatic bone disease. Of the 209 who had had a vitamin D level checked, only 3.8% received more than 600iu vitamin D a day. Only 38.8% patients hada 25-OHD level >30 ng/ml; Serum PTH levels roseas serum 25-OHD concentrations declined to <30 ng/ml. Even in the group of patientswith a serum 25-OHD level >30 ng/ml, four of 74 (5.4%) hadsecondary hyperparathyroidism.”

“This study revealed that vitamin D insufficiency has a highprevalence among breast cancer patients being treated with abisphosphonate for osteoporosis or metastatic bone disease andthat supplementation of calcium and vitamin D is underused inthe care of these patients. This finding suggests that it is probably more appropriateto set the level for vitamin D adequacy to a screening 25-OHDlevel of >30 ng/ml ie >105nmol/L.we advocate routinescreening of the 25-OHD concentration for vitamin D deficiencyin general.”

Now Cohen ea from Columbia University New York question the use of bisphosphonate in younger women with osteoporosis, when easily correctable deficiencies are so often the cause.

And a new Kaiser Permanente community Effectiveness study by Feinstein ea in fact shows that in 10 years to 2006, on bisphosphonates some 1830 elderly women at high risk of osteoporosis fracture had no significant reduction in major fractures.

We know that bisphosphonates require adequate vitamin D levels to work. The bizarre joke is that Big Pharma is even marketing bisphosphonate paired with lowdose vitamin D. Why on earth poison harmless effective vitamin D with a toxin that can cause bone collapse, gullet ulceration and obstruction, toxoderma, muscle damage and arrhythmia?

We know that even oral HT with CEE and progestin reduces hip fractures by up to 40%; but we also see regularly that combined HRT including parenteral testosterone and all the other proven supplements steadily increases bone density into the normal range in the severest osteoporotic, AND reduces especially falls and fractures by reversing frailty.

As Brown says in a comprehensive 2008 review, restoring vitamin D deficiency with 800 instead of 400iu daily already doubles the reduction in fractures, and greatly reduces falls in the elderly. Hence we must agree with her, and Geller and Adams from UCLA 2008, that vitamin D in effective dose – reportedly to a safe meaningful blood level of >35ng/ml ie 100-130nmol/L, in company with appropriate parenteral combined HRT and the other dozen balanced vitamins and minerals, can more than halve both fractures and all other common degenerative disease risks. We have discussed repeatedly in this column that appropriate testosterone- estradiol replacement greatly reduces all-cause morbidity and mortality even in men or women after cancer.

So the question remains: why (except for marketeering, profit motivations) are patients with osteoporosis or cancer metastases being given notoriously toxic bisphosphonates- which have never been shown to be safe let alone beneficial long term – when it has been known for decades that adequate replacement with natural appropriate supplements- including balanced calcium, magnesium, zinc, boron, manganese; vitamins B,C,D & K, and appropriate physiological testosterone and estradiol to restore the healthy balance of healthy youth- and especially vigorous vitamin D3 supplement. 1, 2 – rebuilds and maintains musculoskeletal health..

Osteoporosis is like diabetes, hypertension, obesity, cancer, cardio/neurovascullar, arthritic, mood and dementing diseases, a multi- $billion-dollar a year target for the designer drug industry -let alone the diagnostics and invasive medical industries. For these industries, lucrative drugs, tests and surgery far outweigh the boring counseling about lifestyle and lowcost micronutrient preventatives- which would make designer drugs, costly tests and surgeries – hospitalization- virtually obsolete for medical conditions except for those who live to be the oldest of the old.

The NIH years ago introduced incentives in far higher consultation fees for cardiologists and cardiac surgeons to spend time counseling patients about better diet, lifestyle and medicine use instead of invasive procedures and surgery- which do not address the underlying pathogenesis eg overweight, stress-cortisol, insulin resistance. Such an approach resulted in eg cardiologists Drs Siinatra and Roberts virtually abandoning invasive cardiology since virtually every patient with ischemic heart disease could and can be cured with intensive consulting room management including optimization of designer drugs and curative supplements.

It is apparent that no mainstream physicians bother to publicize this approach to the equally common but far more disabling problem of osteoporotic fractures- which kills or leaves impaired far more patients than vascular disease. eg the the latest reviews of treatments for postmenopausal osteoporosis available as abstract or fulltext on Pubmed- a Canadian consensus 2003 , Hauselmann & Rizzoli 2003 and Cosman 2005 failed to even mention true preventatives beyond futile lone calcium and lowdose vitamin D – despite there being study evidence to support vitamins B6-9-12, C, K, magnesium, zinc, boron, manganese, (fluoride if low in local water), and physiological replacement of deficient testosterone/ DHEA -estradiol.

No-one is going to support trials of combined natural supplements to prevent and treat osteoporosis when the disease industry, as well as the osteoporosis associations which they invariably fund and feed with drug information, all have vested interests in avoiding simple universal combination prevention.

The study from Wang-Gillam et al opens the way for wider class actions 3, 4 by Regulators and patients against the promoters, marketeers and prescribers of all bisphosphonates, since it has always been clear that adequate replacement of natural supplements would have done and do far better. But Regulators are in fact co-conspirators since they allow modern drugs to be widely used without evidence that they are as good as long-used safe and cheap old supplements.

Despite the high cost (in money and suffering) of bisphosphonates and other designer drugs eg Forteo against osteoporosis, no trials have shown that they reduce all-cause mortality – ie unlike natural supplements (which address all common diseases – improving defenses against fractures, depression, infection, cancers, vascular disease, dementia etc, and thus halve premature morbidity and mortality), bisphosphonates’ only action is to -disastrously – stop necessary bone remodeling. It is common cause that the chief causes of osteoporosis- muscle and general frailty, aging’s catabolic dominance- are not aided by designer drugs like bisphosphonates and Forteo; only anabolic agents like parenteral testosterone replacement, vigorous vitamin D and the combination of other micronutrients listed above do so.

Avoidance of this central issue – failure to address underlying pathogenesis and numerous simply correctable micronutritional deficiencies – is the major fraud of teaching, marketing and promoting predominantly designer drugs and technology – in which fraud Regulators, politicians and often academics cravenly conspire, Elaine Feuer’s The FDA War against Humanity. Not for nothing did one of the greatest social philosophers of the 20th century Ivan Illich call organized medicine- the capitalist Disease Industry – Medical Nemesis.

Is it an overstatement to say that bisphosphonates are clearly even worse chronic disaster than statins – where the damage is usually insidious but reversible- or NSAID class drugs- which can simply kill by thrombosis or bleeding; or SSRIs- which can trigger suicide? The other modern drugs (after thalidomide) do not, like bisphosphonates, disfigure and maim.

The reviews and trials of bisphosphonates the last year are especially alarming for zoledronic acid (ZA Reclast / Zometa)

Today’s FDA (Grewal) last month reports that ZA and Aredia give an osteonecrosis (O.N) risk of about 1:10 000 patients; alendronate a risk of 0.7/ 100 000 patient years.

this year Italy (Ibrahim) reports an incidence of 1.5% ONJ in 500 cancer patients over 4yrs- and all those patients were treated with ZA.

Harvard Dental School (Wessel) this year reports 30 cases of O.N of the jaw ONJ over 4 years – all on ZA.

But Univ Arizona (Hess) this year reports99 cases of ONJ after bisphos in patients without cancer- 85 for OP, 10 for Pagets. 87% were women and 83%hadoral notiv BNP.

The international HORIZON Z.A.osteoporosistrials last year reported 1 case of O.Nin each 2500 arm of trialists on ZA or placebo (mean 74yrs (65-85yrs) treated with annual ZA versus placebo injection; there was 35% reduction in fracture rate at mean followup 1.9years in those enrolled after hip fracture ie tertiary prevention ;

There was however no significant difference in major adverse events or non-fracture deaths (the causes of death of the majority. were not reported). However, serious atrial fibrillation was 3 times more common in the month after ZA than after placebo. By 1.9yrs after the hip fracture and starting ZA there were fewer deaths on ZA 4.5%pa than placebo 6.7%; but in the slightly younger and fitter majority ie those without prior hip fracture, by 3 yrs, there were 16% more deaths on ZA (1.13%pa%) than placebo(0.97%pa%).

These 2007 Horizon trials thus highlight that delaying prevention till the hip collapses more than trebles the deathrate .

What they mysteriously neglect to report is the quality of life, mobility after major osteoporotic fracture- when it is common cause that waiting for major disease before starting prevention is disastrous- sudden death, stroke, dementia; or that at best 20% of patients recover full health and mobility after hip fracture.

However, (as usual with commercially sponsored trials to promote a new drug – ie seeding trials) baseline conventionally proven natural therapies were severely limited, probablyto falsely exaggerate the benefit of the trial drug: so (while almost half were apparently on raloxifene), all including the placebo arm were given a baseline regime only of vitamin D and modest dose calcium.

While it is common cause that quality of life QOL is greatly improved by appropriate HRT in the menopause transition- the midlife decade of menopause symptoms ,

longterm QOL outcome is conveniently not mentioned in any bisphosphonate papers that span the progressively more riskydecades after the midsixties – although this QOL attribute for ZA is a main goal that Novartis mentions in it’s registration motivation ” The unique once-yearly dosing of this medicine has the potential for significant compliance benefits and improved quality of life for women with osteoporosis.”

Despite the fact that trials of bisphosphonates for osteoporosis started over 20 years ago, no such claim of improved mobility and QOL long term is made, so there cannot have been any significant improvement shown. There are exactly two small trials, from Italy and Turkey, that lasted one year looking at QOL, that showed improvement in QOL on (alendronate or nerindronate or calcitonin) plus calcium/vit D versus calcium/vit D alone. Short term study- one year – says nothing about the average 35yrs of life expectancy after the perimenopausal midlife decade. .

The bisphosphonate trials also blithely omit that the top risk factor for osteoporotic fractures is not bone density but overall physical – frailty, falls; and while major fractures are common in the old, they dont happen,if the patient dies early, or they matter little if the patient is first disabled (before fracturing) by far more common cardiovascular-stroke problems or dementia.

Nobody can claim, show that bisphosphonates, SERMS, tibolone, calcitonin, strontium have any significant long term benefit on overall premature major diseases of aging and mortality. Unlike appropriate HRT, or fish oil, or metformin, or vigorous other combination of natural supplements (vitamins, minerals and biologicals including herbs) , no modern chronic designer patent drug for chronic prevention has been shown to significantly reduce all-cause morbidity and mortality – especially diabetes, CVD-stroke, osteoarthritis, fractures, major depression and dementia. .

So there is no justification or need to take bisphosphonates or any other newer patent drugs for osteoporosis – and why take the risk of bisphosphonate arrhythmia, toxicoderma or osteonecrosis?

No trials have ever been published showing that biphosphonates do overall good long term for osteoporosis- ie reduce all-cause mortality, and reduce hip fracture, without toxicity.
Biphosphonate Osteonecrosis of long bones was already published in 1995, and from 2001 in USA.
So their heavy marketing, and prescription like vitamins, causing the epidemic of devastating osteonecrosis, makes the prescribers, manufacturers, dispensers and Regulators – eg the FDA -criminally liable.

Effects of continuing ALENDRONATE after 5 years of treatment: Fracture Intervention Extension to 10yrs
JAMA. 2006 Black, Cummings UCSF. (who funds them?!)
In 1099 women re-randomized to alendronate or placebo for a further 5 years (1998-2003):

The osteonecrosis problem may be 95% with iv BPNs (Urade) – orally BNPs like HRT are absorbed below 10%;
but
as with oral HRT, the problem may be both total dose absorbed, and total length of exposure –BPNs (given over perhaps a year iv) bind to bone for 10yrs. Fosamax is swallowed for 3-5yrs.
Jones & Wilkinson’s (April 2006 NHS review of oral BPN adversity) found that adherence on oral BPNs is only around 50% by 3 years due to adversity – GIT, musculoskeletal, skin….
and when stopped, BMD is maintained for up to 2 yrs due to bound Testosterone (unlike estrogen).

Is there (as there was with tobacco, Premarin & Vioxx)
a BMD industry OSTEOPOROSIS FRACTURE DECEPTION?

By contrast,
permanent appropriate TRT in men and T+ E2RT in women can prevent eg the up to 40% bone loss that occurs in 6 months on corticosteroids (Studd 1989),

restore up to 26% of lost BMD in critical areas like Ward’s triangle ie (the hipbone’s neck);

of the 6 published RCTs that have given testosterone replacement (with or without estrogen) for 1-2 years post menopause, 5 showed that testosterone gave better increase in BMD than estrogen alone.
In the 6th and oldest study (Studd 1992) in women both with and without hysterectomy, adding implants of testo 75mg 6mthly to Esto 100mg 6mthly made no difference over esto alone, possibly because the of the supraphysiological esto level attained (mean ~1.9nmol/L per Studd 2006) and the followup of only 1year.

In the 7th trial of only 6 months(2005), no improvement was seen in BMD on either esto alone or on Esto + testo- but it used oral HRT; lean mass increased only on the combination- so these women would have been less prone to falls and fractures. .

On the baker’s dozen of natural supplements, we have seen bone density increasing steadily by 1% a year – slightly faster in spine than hip- over 15 years in eg a severely osteoporotic woman with chronic active rheumatoid arthritis on prednisone.

After osteonecrosis the results with hyperbaric oxygen added to the natural supplements appear useful to justify it’s use to salvage whats left ..

HRT AND FRACTURES:

IN the Women’s Health Initiative,

the fracture rate in those with womb was 0.15%pa,
and E+P reduced this by 34% over 5.6yrs;

in those post hysterectomy ie longer without hormones,
the fracture rate was 0.17%pa,
and E alone reduced this by 39% ie 60% still had long bone fractures.

No trials have measured fracture rate on TRT in women;
but we never see women on TRT have spontaneous limb fracture.

Use of platelet-rich plasma in the management of oral biphosphonate-associated osteonecrosis of the jaw: a report of 2 cases. J Oral Implantol. 2007;33:371-82 Lee CY, ea
Bisphosphonates (BP) are nonhormonal medications used in the treatment of various bone malignancies and metabolic conditions. Since 2003, there have appeared a significant and growing number of articles in the worldwide medical and dental literature describing the complication of an osteonecrosis of the jaws associated with the intravenous and, most recently, the oral form of BP medication that has been refractory to any definitive form of treatment. The authors have successfully managed 2 patients taking the oral form of BP with adjunctive treatment using platelet-rich plasma (PRP), and in one case with hyperbaric oxygen (HBO). We were able to obtain complete remission in each case, which is defined as resolution of pain and complete closure of exposed bone in the jaws. The purpose of this report is to describe a treatment protocol and the rationale for using PRP and HBO to obtain complete remission of this new pathologic condition.

Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: a case series.J Oral Maxillofac Surg. 2007 Jul;65(7):1275-6. Freiberger JJ, Padilla-Burgos R, Chhoeu AH, Kraft KH, Boneta O, Moon RE, Piantadosi CA.Duke University Medical Center, Divers Alert Network, Durham,.
PURPOSE: Bisphosphonate (BP)-associated osteonecrosis of the jaw (ONJ) is an emerging problem with few therapeutic options. Our pilot study of BP-ONJ investigated a possible role for hyperbaric oxygen (HBO(2)) therapy. PATIENTS AND METHODS: A total of 16 patients, ranging in age from 43 to 78 years, with BP-ONJ were treated with adjunctive HBO(2) between July 2003 and April 2006. Staging was based on the size and number of oral lesions. Clinical response after treatment and at distant follow-up; the odds of remission, stabilization, or relapse; and time to failure analysis were calculated. RESULTS: The median time on BP therapy before appearance of ONJ symptoms was 18 months, and that from symptom onset to HBO(2) therapy was 12 months. Fourteen of 16 patients (87.5%) improved in stage. The size and number of ONJ lesions were decreased after HBO(2) therapy (P < .001 and P = .008, respectively; Wilcoxon signed-rank test). Immediately after HBO(2) therapy, 7 of 16 patients (44%) were in remission and 8 (50%) had stabilized; however, stabilization without remission was sustained in only 2 patients. At follow-up, 10 of the patients (62.5%) were still in remission or had stabilized. The 7 patients who continued on BP treatment during HBO(2) therapy had a shorter time to failure (8.5 months; 95% confidence interval [CI] = 7.1 to 9.8) than those who discontinued the drug (20.1 months; 95% CI = 17.5 to 23.9; P = .006 by the log-rank test). Clinical response was not associated with cancer type or malignancy remission status. CONCLUSIONS: Adjunctive HBO(2) therapy may benefit patients with BP-ONJ; however, the outcome is improved with cessation of BP administration.

3: Am J Otolaryngol. 2007 May-Jun;28(3):158-63.
Osteonecrosis of the jaws due to bisphosphonate use. A review of 60 cases and treatment proposals.
Magopoulos C, Karakinaris G, Telioudis Z, Vahtsevanos K, Dimitrakopoulos I, Antoniadis K, Delaroudis S. Aristotle University, Thessaloniki, Greece.
PURPOSE: Bisphosphonates are compounds used in the treatment of various metabolic and malignant bone diseases. In the last two and a half years, there has been a striking increased referral of patients with exposed necrotic jawbone, mostly after several teeth extractions. The only clinical feature common in all patients was the use of bisphosphonates in the treatment of bone diseases. PATIENTS AND METHODS: We performed a retrospective multicentric study of 60 patients with necrotic bone lesions of the jaws of various extent from July 2003 to October 2005. The necrotic bone involved the maxilla (37%), the mandible (50%), or both (13%). The bisphosphonate administered was mostly zoledronate. The management of the patients included cessation of bisphosphonate therapy for more than 6 months, long-term antibiotics, hyperbaric oxygen administration in some cases, and various surgical restorative procedures. RESULTS: The implementation of the treatment protocol in 7 patients so far lead to high cure rates, whereas surgical restoration of the defect without previous cessation of bisphosphonate therapy had discouraging results. CONCLUSIONS: Clinicians and dentists should have in mind this new complication of bisphosphonate administration to identify and treat osteonecrosis of the jaws.